Gonadotropin releasing hormone (GnRH, also referred to as LHRH) is a decapeptide consisting of 10 amino acids, which is produced in the hypothalamus and known to control secretion of luteinizing hormone (LH), follicle stimulating hormone (FSH) and the like through receptors considered to be present in the anterior pituitary, based on which GnRH shows a variety of physiological activities such as ovulation induction and the like. Therefore, specific and selective antagonists or agonists to these receptors control hormone action of GnRH produced from the hypothalamus, and control secretion of anterior pituitary hormone such as LH, FSH and the like. Therefore, secretion of estrogen in females and of testosterone in males is suppressed and a prophylactic or therapeutic effect on sex hormone-dependent diseases can be expected.
For example, leuprorelin acetate, which is an agonist of gonadotropin releasing hormone receptor, has 20 to 100 times the activity of natural GnRH, and is a compound that is not easily metabolized. Repetitive administration thereof causes down regulation of GnRH receptors and decreases release and production of gonadotrophic hormone in the pituitary gland, which is demonstrated by, for example, reduced reactivity to gonadotrophic hormone and lowered productivity of testosterone to a sterilization level in the testes, and lowered productivity of estrogen in the ovaries. As a result, it can be a useful prophylactic or therapeutic agent for these hormone-dependent diseases, such as prostate cancer, prostatic hypertrophy, masculinism, hypertrichiasis, male-pattern baldness, male infantile precocity, female infantile precocity, precocious puberty, breast cancer, uterine cancer, mastopathy, hysteromyoma, endometriosis and the like. In fact, leuprorelin acetate has been used widely in clinical situations as a therapeutic drug for prostate cancer, breast cancer, endometriosis, hysteromyoma, precocious puberty and the like.
However, certain kinds of cancers acquire an ability to grow even at an extremely low concentration of hormone (e.g., androgen at sterilization level). The present invention aims at provision of a pharmaceutical agent and a prophylactic or therapeutic method based on an LHRH agonist or antagonist or a silt thereof that improves a prophylactic or therapeutic effect on various hormone-dependent diseases.